taurochenodeoxycholic-acid and Stomach-Neoplasms

Taurochenodeoxycholic acid (TCDCA) is the principal ingredient of Compound Shougong Powder. Despite traditional Chinese medicine (TCM) research demonstrates that Compound Shougong Powder can restrict tumor growth, whether TCDCA exerts a role in suppressing cancer as the major ingredient of Compound Shougong Powder remains unknown. This study aims to clarify the regulatory mechanism of TCDCA on gastric cancer. Gastric cancer cells SGC-7901 were cultured to investigate the effects of TCDCA on proliferation and apoptosis. Furthermore, a subcutaneously implanted tumor model was established using SGC-7901 cells in BALB/C nude mice and tumor volume was measured under low and high dose treatment of TCDCA. Cell proliferation, apoptosis, and invasion were subjected to 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flow cytometry, and transwell assay. Differentially expressed genes were screened by transcriptome sequencing. Nude mouse tumorigenicity assay was initiated to identify the effect of TCDCA on both tumor volume and weight, and the expression of candidate genes screened by transcriptome sequencing was determined by real-time fluorescence quantification (qPCR) and Western blot. The experiments revealed that TCDCA could significantly inhibit the proliferation and invasion of gastric cancer cells and induce apoptosis of these cells. Meanwhile, test findings via in vivo indicated that TCDCA severely diminished the volume and weight of tumors. This study first demonstrated that TCDCA inhibited the proliferation and invasion of gastric cancer and induced apoptosis, which is expected to serve as an experimental basis for the application of TCM in tumor therapeutic options. PRACTICAL APPLICATIONS: Through this study, the inhibitory effect of Taurochenodeoxycholic acid on gastric cancer can be clarified, which provides a new research basis for the application of traditional Chinese medicine (TCM) and TCM monomer in cancer. In addition, this study can further promote the research and application of Chinese traditional medicine, which has important application value and economic benefits.

Topics: Animals; Apoptosis; Cell Proliferation; Mice; Mice, Inbred BALB C; Mice, Nude; Powders; Stomach Neoplasms; Taurochenodeoxycholic Acid

Bile acids have been suggested to play an important role in the etiology of colon and gastric cancer after gastrectomy, but the molecular biology of these effects is poorly understood. We evaluated the effect of different bile acids on human gastric and colon carcinoma cells and identified genes by RNA arbitrarily primed PCR for differential display that are modulated following treatment with hydrophobic bile acids. Thioredoxin reductase (TR) mRNA was upregulated after treatment with taurochenodeoxycholic acid (TCDCA) in St 23132 cells. This raised the question whether deoxycholic acid (DCA) would have regulative effects on TR in HT-29 cells. After an incubation time of 6 h with DCA, TR mRNA expression was increased up to threefold. Ursodeoxycholic acid had no influence on TR mRNA expression. The upregulation of TR after DCA incubation was almost identical to incubation with 12-O-tetradecanoylphorbol-13-acetate. This implies that hydrophobic bile acids mediate oxidative stress in gastrointestinal cancer cells, which was confirmed by measurement of oxidative burst after treatment with DCA. The results suggest that hydrophobic bile acids induce oxidative stress in gastrointestinal cancer resulting in a compensatory upregulation of TR mRNA, one of the key components in the complex anti-oxidant defense system within eukaryotic cells. The activation of at least parts of the redox signaling system is potentially related to the cytotoxicity and the stimulation of the cell death machinery induced by toxic bile acids.

Topics: Base Sequence; Colonic Neoplasms; DNA Primers; Flow Cytometry; Gene Expression Regulation, Neoplastic; HT29 Cells; Humans; Oxidative Stress; Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Taurochenodeoxycholic Acid; Thioredoxin-Disulfide Reductase; Up-Regulation